| Staff Details | ||||
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| Personal Information | ||
| Name | Khan, Amir Rafiq | |
| Main Department | Biochemistry | |
| College Title | Lecturer | |
| amir.khan@tcd.ie | ||
| College Tel | +353 1 896 3868 | |
| Web | http://people.tcd.ie/amirrafk | |
| Description of Research Interests |
| The experimental goal is determination of structures of Rabs with their effector proteins by X-ray crystallography. The first project will involve Rab6, which regulates the forward and retrograde transport pathways at the level of Golgi membranes. The downstream effects of Rab6 are mediated by Rab6IP1, a 1263-residue Rab6IP1 that contains several novel domains for which there is no structural information in the Protein Data Bank. The second project involves Rab11, which is involved in endocytic recycling processes, as well as endosome-to-Golgi trafficking. One of its effectors is FIP2, which belongs to a family of proteins that contain a conserved C-terminal Rab-binding domain. The structures of these effectors may have novel folds, and the complexes with their respective Rabs are likely to demonstrate novel modes of interaction. In addition, the structure of the complex will enable a generalization of the mechanism of Rab family-mediated signaling, since the domains observed in Rab6IP1 are also found in a variety of other mammalian proteins. |
| Research Interests | |||
| CONGENITAL HEMANGIOPERICYTOMA | EXTERNAL CAROTID ARTERY LIGATION | LIFE-THREATENING HEMORRHAGE |
| Research Projects | |
| Project title | X-ray Crystallographic Studies of Poxvirus-Mediated Antagonism of TLR signaling |
| Summary | Toll-like receptors (TLRs) are essential components of innate immunity against bacterial and viral pathogens. The ten TLRs in humans recognize broad types of pathogen associated molecular patterns (PAMPs) including nucleic acids and lipopolysaccharides. The signaling cascade is initiated by their intracellular Toll-like/interleukin-1 receptor (TIR) domains which oligomerize and recruit TIR-containing adaptor proteins such as MyD88 to mediate downstream events. Viruses often attenuate immune responses, and recently, vaccinia virus proteins A46R, A52R and K7R have been shown to antagonize TLR signaling pathways. Interestingly, A46R contains a putative TIR domain that binds to MyD88 and blocks TLR activation, in contrast to the TIR domains of TLRs which promote the signaling cascade. The project described here will involve X-ray crystallographic studies of poxvirus proteins A46R, A52R and K7R alone and in complex with their cellular targets in order to understand the molecular basis for antagonism of TLR signaling. |
| Funding Agency | Science Foundation Ireland |
| Programme | SFI Frontiers Programme |
| Type of Project | |
| Date from | 1/10/2005 |
| Date to | 31/9/2008 |
| Person Months | 72 |
| Publications |
| Peer Reviewed |
| Shun-ichiro Oda, Martina Schroder, Amir R. Khan, Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7, Structure (Cell Press), 17, 2009, p1528 - 1537 | |
| Jagoe WN, Lindsay AJ, Read RJ, McCoy AJ, McCaffrey MW & Khan AR, Crystal structure of Rab11 in complex with Rab11 Family Interacting Protein 2, Structure (Cell Press), 14, (8), 2006, p1273 - 1283 Notes: [PMID: 16905101 ] Url Alt. Url DOI |
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| Chen M, Stafford W, Diedrich G, Khan AR and Bouvier M, A characterization of the lumenal region of human tapasin reveals the presence of two structural domains., Biochemistry, 41, (49), 2002, p14539 - 14545 Notes: [PMID: 12463753] Url DOI |
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| Khan AR, Khazanovich-Bernstein N, Bergmann EM & James MNG , Structural aspects of the activation pathways of aspartic protease zymogens and viral 3C protease zymogens. , Proc Natl Acad Sci USA , 96, (20), 1999, p10968 - 10975 Notes: [PMID: 10500110] Url |
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| Khan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA & James MNG, Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes. , Biochemistry, 37, (48), 1998, p16839 - 16845 Notes: [PMID: 9836576 ] Url DOI |
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